ArticlePloS one2017
α-Klotho expression determines nitric oxide synthesis in response to FGF-23 in human aortic endothelial cells.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 47 citations in OpenAlex.
- Converging neurotrophic-immune signaling in autism spectrum disorder: integrative roles of klotho, GDNF/GFRA-1, IGF-1 and GLP-1 pathways.Metabolic brain disease · 2026Review
- Olive Leaf Extract Added to Losartan Treatment Improved Klotho/Wnt/β-Catenin Signaling in Hypertensive Rats with Focal Segmental Glomerulosclerosis.Antioxidants (Basel, Switzerland) · 2026Article
- Association between the serum Klotho levels and diabetic kidney disease: results from the NHANES 2007-2016 and Mendelian randomization study.Journal of diabetes and metabolic disorders · 2025Article
- Adipokines and Vascular Modulators in CKM: Emerging Biomarkers as Diagnostic and Therapeutic Targets.International journal of molecular sciences · 2025Review
- The Anti-Inflammatory Actions of Soluble Klotho in Brain Aging and Its Main Associated Diseases.International journal of molecular sciences · 2025Review
- Article
- Preeclampsia as a Study Model for Aging: The Klotho Gene Paradigm.International journal of molecular sciences · 2025Review
- The mechanism by which FGF23/FGFR-1 activates NOX2-ROS in vascular endothelial cells in the context of severe heat stroke-induced acute lung injury.Burns & trauma · 2025Article
- Klotho protein: a new insight into the pathogenesis of essential hypertension.Clinical hypertension · 2024Article
- Self-control study of multi-omics in identification of microenvironment characteristics in urine of uric acid stone.Scientific reports · 2024Article
- The role of Klotho and sirtuins in sleep-related cardiovascular diseases: a review study.npj aging · 2024Review
- AMP-dependent kinase stimulates the expression of αKlotho.FEBS open bio · 2024Article
- Review
- Fibroblast growth factor 23 inhibition attenuates steroid-induced osteonecrosis of the femoral head through pyroptosis.Scientific reports · 2024Article
- Potential Intersections between lncRNA, Vascular Cognitive Impairment, and Immunization Strategies: Insights and Future Directions.Vaccines · 2024Review
- FGF23 and klotho at the intersection of kidney and cardiovascular disease.Nature reviews. Cardiology · 2024Review
- The dysregulation of plasma miR-497/FGF23 axis, and its association with clinical characteristics and major adverse cardiovascular event in female premature acute coronary syndrome patients.Irish journal of medical science · 2023Article
- ADAM10 and ADAM17, Major Regulators of Chronic Kidney Disease Induced Atherosclerosis?International journal of molecular sciences · 2023Review
- The role of Klotho and FGF23 in cardiovascular outcomes of diabetic patients with chronic limb threatening ischemia: a prospective study.Scientific reports · 2023Article
- Perioperative variation in serum FGF-23 level and its correlation with MACCE risk in unprotected left main coronary artery disease patients receiving coronary artery bypassing grafting.Frontiers in surgery · 2022Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endothelial cells (ECs) express fibroblast growth factor (FGF) receptors and are metabolically active after treatment with FGF-23. It is not known if this effect is α-Klotho independent or mediated by humoral or endogenous endothelial α-Klotho. In the present study, we aimed to characterize EC α-Klotho expression within the human vascular tree and to investigate the potential role of α-Klotho in determining FGF-23 mediated EC regulation. Human tissue and ECs from various organs were used for immunohistochemistry and Western blot. Primary cultures of human aortic endothelial cells (HAECs) and human brain microvascular endothelial cells (HBMECs) were used to generate in vitro cell models. We found endogenous α-Klotho expression in ECs from various organs except in microvascular ECs from human brain. Furthermore, FGF-23 stimulated endothelial nitric oxide synthase (eNOS) expression, nitric oxide (NO) production, and cell proliferation in HAECs. Interestingly, these effects were not observed in our HBMEC model in vitro. High phosphate treatment and endothelial α-Klotho knockdown mitigated FGF-23 mediated eNOS induction, NO production, and cell proliferation in HAECs. Rescue treatment with soluble α-Klotho did not reverse endothelial FGF-23 resistance caused by reduced or absent α-Klotho expression in HAECs. These novel observations provide evidence for differential α-Klotho functional expression in the human endothelium and its presence may play a role in determining the response to FGF-23 in the vascular tree. α-Klotho was not detected in cerebral microvascular ECs and its absence may render these cells nonresponsive to FGF-23.
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Registered trials
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